Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue transglutaminase (tTG) activity was used to test the potent regulatory role of vasoactive intestinal peptide (VIP) on Retinoic Acid-induced effect in human neuroblastoma cell line. The comparison between both differentiation and cell death related to tissue transglutaminase was discussed in this model. VIP alone was a potent differentiating agent in SK-N-SH cells but in the presence of retinoic acid (RA), this peptide rather potentiates RA-induced tTG activity which is now considered as an apoptosis marker in neuroblastoma cell line. This paper demonstrated an additional neuromodulator role for VIP.
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PMID:VIP potentiates retinoic-acid effect on tissue transglutaminase activity in human neuroblastoma, the SK-N-SH cells. 809 34

The modulation of inward K+ conductances was studied during neuronal differentiation of human SH-SY5Y neuroblastoma cells. Under standard culture conditions, these cells express the herg gene, and the HERG current is the main inward K+ current regulating their Vrest. After 10-20 days exposure to Retinoic Acid (RA), SH-SY5Y cells showed, in addition to HERG currents, a novel current characterized by inward rectification, dependence on the extracellular K+ concentration, and blockade by Cs+ and Ba2+, the main features of the IRK1 current. The appearance of this current is accompanied by a strong hyperpolarisation of Vrest. RT-PCR experiments confirmed that a transcript of the IRK1 (Kir 2.1) gene actually appears in SH-SY5Y cells treated for 10-20 days with RA. On the whole, data here presented demonstrate that RA-induced neuronal differentiation of neuroblastoma cells is accompanied by the switch from a HERG-driven to a IRK1-driven control of Vrest, similarly to what happens in normal differentiating neurons; however, in tumor cells, this switch does not imply the abolition of HERG channel expression.
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PMID:Long-term exposure to retinoic acid induces the expression of IRK1 channels in HERG channel-endowed neuroblastoma cells. 953 29

The most widely used retinoids include topical tretinoin (Retin-A), adapalene (Differin), topical tazarotene (Tazorac), isotretinoin (Accutane), and acitretin (Soriatane). This article will review new uses and developments in tazarotene (its failure to secure FDA approval in oral form for psoriasis), adapalene (its new 0.3% gel form and use in rosacea), alitretinoin (its use in photoaging), bexarotene (its use for psoriasis and chronic hand dermatitis), isotretinoin (the IPledge program, its use for neuroblastoma and branded formulation pharmacological superiority to generics), and retinoic acid metabolism-blocking agents (RAMBAs) (liarazole use for ichthyosis and psoriasis).
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PMID:Schools of pharmacology: retinoid update. 1703 62

Retinoic Acid (RA) has been shown to control growth and induce differentiation in a number of human neuroblastoma (NB) cell lines. However, a number of NB cell lines may be termed resistant to RA as they fail to growth arrest and differentiate. In studying the mechanism mediating RA-resistance, we noted that invariably RA-resistant NB cell lines constitutively express Insulin-like Growth Factor 2 (IGF2) (Gaetano, 1991b). The NB cell line LAN-1-15N (15N) represented an interesting model in which to study the development of RA-resistance as initially 15N cells are growth arrested by RA, however with prolonged culture (8-10 days) cells begin to proliferate. Coincidentally, RA induces IGF2 mRNA and protein secretion in 15N NB cells (Matsumoto, 1992). In this study we isolated RA-resistant 15N cell lines and analyzed their growth properties and changes in cell cycle related (cdc2, cdk2, cyclins A, B, D and E) and early response (fos and jun) gene expression to evaluate the role IGF2 may play in mediating RA resistance. We found that exogenous IGF2 stimulates growth in 15N and is capable of altering RA induced inhibition of NB cell growth. Finally we show that by blocking the Insulin-like Growth Factor Receptor (IGF1(R)) with a monoclonal antibody (alpha-IR3) in the presence of RA the growth of RAR cell lines could be completely blocked. These data are consistent with the concept that signals by IGF2 and transduced via the IGF1(R) can mediate resistance to the growth inhibiting properties of RA.
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PMID:Signals transduced via insulin-like growth factor I receptor (IGF(R)) mediate resistance to retinoic acid-induced cell growth arrest in a human neuroblastoma cell line. 1718 6

There are a number of factors relating to the clinical pharmacology of 13-cis-Retinoic Acid (13-cisRA) which, taken together, provide a strong case for the potential benefit of a therapeutic monitoring approach to ensure that uniform plasma concentrations of 13-cisRA are achieved in all patients. Firstly, low dose, continuous use of 13-cisRA has been shown to provide limited or no clinical benefit in neuroblastoma patients, whereas a high-dose, intermittent regimen resulted in a significant improvement in event-free survival. This suggests that dose levels and therefore plasma concentrations of drug are important determinants of 13-cisRA efficacy. Secondly, the currently used 13-cisRA dosing regimen of 160 mg/m(2)/day results in a >10-fold variation in plasma concentrations, with plasma concentrations observed in a significant percentage of patients below those required for activity in neuroblastoma cells in vitro. Importantly, there would appear to be limited intra-patient variation in 13-cisRA plasma concentrations, i.e. those patients with lower 13-cisRA plasma concentrations following a single dose of 13-cisRA are likely to have similarly low concentrations following all doses of 13-cisRA on subsequent courses. As 13-cisRA is given as chronic treatment, those patients experiencing lower plasma concentrations on the current dosing regimen will potentially be exposed to sub-therapeutic concentrations of drug for the entire 6 month treatment period. While this type of pharmacokinetic monitoring approach may prove to be beneficial in the short term, an increased knowledge of pharmacogenetic factors influencing to the metabolism of 13-cisRA may ultimately allow us to identify patients who may be less likely to benefit from treatment due to an increased rate of parent drug metabolism. In this respect, pharmacogenetic studies assessing the relative expression levels or mutations in enzymes such as cytochrome P450 (CYP) and particularly CYP26 are needed to assess any potential association with rate of metabolism in vivo.
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PMID:Pharmacokinetics and pharmacogenetics of 13-cis-retinoic acid in the treatment of neuroblastoma. 1758 7

Possible effects of interaction (cross-talk) between signaling pathways is studied in a system of Reaction-Diffusion (RD) equations. Furthermore, the relevance of spontaneous neurite symmetry breaking and Turing instability has been examined through numerical simulations. The interaction between Retinoic Acid (RA) and Notch signaling pathways is considered as a perturbation to RD system of axon-forming potential for N2a neuroblastoma cells. The present work suggests that large increases to the level of RA-Notch interaction can possibly have substantial impacts on neurite outgrowth and on the process of axon formation. This can be observed by the numerical study of the homogeneous system showing that in the absence of RA-Notch interaction the unperturbed homogeneous system may exhibit different saddle-node bifurcations that are robust under small perturbations by low levels of RA-Notch interactions, while large increases in the level of RA-Notch interaction result in a number of transitions of saddle-node bifurcations into Hopf bifurcations. It is speculated that near a Hopf bifurcation, the regulations between the positive and negative feedbacks change in such a way that spontaneous symmetry breaking takes place only when transport of activated Notch protein takes place at a faster rate.
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PMID:Study and simulation of reaction-diffusion systems affected by interacting signaling pathways. 1894 3

In Drosophila, the CASZ1 (castor) gene encodes a zinc finger transcription factor and is a neural fate-determination gene. In mammals, the CASZ1 gene encodes two major isoforms, CASZ1a with 11 zinc fingers and CASZ1b with 5 zinc fingers. CASZ1b is more evolutionally conserved since it is the only homologue found in drosophila and Xenopus. Our previous study showed that full length CASZ1 (CASZ1a) functions to suppress growth in neuroblastoma tumor. However, the function of CASZ1b isoform in mammals is unknown. In this study, realtime PCR analyses indicate that mouse CASZ1b (mCASZ1b) is dynamically expressed during neurogenesis. CASZ1b and CASZ1a co-exist in all the neuronal tissues but exhibit distinct expression patterns spatially and temporally during brain development. CASZ1b and CASZ1a expression is coordinately upregulated by the differentiation agent Retinoic Acid, as well as agents that modify the epigenome in neural crest derived neuroblastoma cell lines. In contrast CASZ1b is down regulated while CASZ1a is upregulated by agents that raise intracellular cAMP levels. CASZ1b and CASZ1a have no synergistic or antagonistic activities on the regulation of their target NGFR gene transcription. Specific restoration of CASZ1b in NB cells suppresses tumor growth in vitro and in vivo. Consistent with its function role, we find that low CASZ1b expression is significantly associated with decreased survival probability of neuroblastoma patients (p<0.02). This study indicates that although their mechanisms of regulation may be distinct, both CASZ1b and CASZ1a have largely redundant but critical roles in suppressing tumor cell growth.
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PMID:CASZ1b, the short isoform of CASZ1 gene, coexpresses with CASZ1a during neurogenesis and suppresses neuroblastoma cell growth. 2149 Sep 19

Isotretinoin (13-cis-retinoic acid; 13-cisRA) has been shown to significantly improve survival for children with high-risk neuroblastoma. Pharmacokinetics of isotretinoin may be negatively affected by the mode of drug administration and the dosing formula.
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PMID:Targeted isotretinoin in neuroblastoma: kinetics, genetics, or absorption. 2308 9

Some experimental evidences of the procedure defined as electro-magnetic information delivery, mediated through aqueous system, have accumulated in the last two decades. The present work is based on the hypotheses that an aqueous system like those enfolded in livings, could play an additional synergic role in modulating biological functions. Aqueous system could generate dissipative structures under appropriate patterns of electromagnetic signals providing basis for storing and retrieving biologic activities. External electro-magnetic stimuli in resonant conditions with some of the coherent domains of water can induce dipole moments re-patterning in a way that these structure start to oscillate coherently each other generating a new phase correlation. This procedure allows to an external electro-magnetic stimulus to be stored, translated and transferred by the aqueous systems to the biological target, driving selectively their endogenous activity mimicking the effect of a specific source molecule. Signals from a chemical differentiation agent such as Retinoic Acid (RA) was captured and transferred to the target culture medium of Neuroblastoma Cell Line (LAN-5) and the proliferation rate was assessed, in order to investigate cell responses to electromagnetic information system.
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PMID:Electromagnetic information delivery as a new tool in translational medicine. 2535 8

Neuroblastoma (NB), an embryonal tumour of the sympathetic nervous system, is thought to originate from undifferentiated neural crest cells and is known to exhibit extremely heterogeneous biological and clinical behaviors. Occurring in very young children, the median age at diagnosis is 17 months and it accounts for 10% of all pediatric cancer mortalities. The standard treatment regimen for patients with high-risk NB includes induction and surgery followed by isotretinoin or Accutane (13-cis retinoic acid) treatment, which is shown to induce terminal differentiation of NB cells. However, molecular regulators that maintain an undifferentiated phenotype in NB cells are still poorly understood.
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PMID:Revealed: The spy who regulates neuroblastoma stem cells. 2548 1


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